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Acute myeloid leukemia (AML), a heterogeneous and aggressive blood cancer, does not respond well to single-drug therapy. A combination of drugs is required to effectively treat this disease. Computational models are critical for combination therapy discovery due to the tens of thousands of two-drug combinations, even with approved drugs. While predicting synergistic drugs is the focus of current methods, few consider drug efficacy and potential toxicity, which are crucial for treatment success. To find effective new drug candidates, we constructed a bipartite network using patient-derived tumor samples and drugs. The network is based on drug-response screening and summarizes all treatment response heterogeneity as drug response weights. This bipartite network is then projected onto the drug part, resulting in the drug similarity network. Distinct drug clusters were identified using community detection methods, each targeting different biological processes and pathways as revealed by enrichment and pathway analysis of the drugs' protein targets. Four drugs with the highest efficacy and lowest toxicity from each cluster were selected and tested for drug sensitivity using cell viability assays on various samples. Results show that the combinations of ruxolitinib-ulixertinib and sapanisertib-LY3009120 are the most effective with the least toxicity and best synergistic effects on blasts.

Background and purpose — Periprosthetic joint infection (PJI) is a devastating complication and more information on risk factors for PJI is required to find measures to prevent infections. Therefore, we assessed risk factors for PJI after primary total hip arthroplasty (THA) in a large patient cohort. Patients and methods — We analyzed 33,337 primary THAs performed between May 2014 and January 2018 based on the Finnish Arthroplasty Register (FAR). Cox proportional hazards regression was used to estimate hazard ratios with 95% confidence intervals (CI) for first PJI revision operation using 25 potential patient- and surgical-related risk factors as covariates. Results — 350 primary THAs were revised for the first time due to PJI during the study period. The hazard ratios for PJI revision in multivariable analysis were 2.0 (CI 1.3–3.2) for ASA class II and 3.2 (2.0–5.1) for ASA class III–IV compared with ASA class I, 1.4 (1.1–1.7) for bleeding > 500 mL compared with < 500 mL, 0.4 (0.2–0.7) for ceramic-on-ceramic bearing couple compared with metal-on-polyethylene and for the first 3 postoperative weeks, 3.0 (1.6–5.6) for operation time of > 120 minutes compared with 45–59 minutes, and 2.6 (1.4–4.9) for simultaneous bilateral operation. In the univariable analysis, hazard ratios for PJI revision were 2.3 (1.7–3.3) for BMI of 31–35 and 5.0 (3.5–7.1) for BMI of > 35 compared with patients with BMI of 21–25. Interpretation — We found several modifiable risk factors associated with increased PJI revision risk after THA to which special attention should be paid preoperatively. In particular, high BMI may be an even more prominent risk factor for PJI than previously assessed. publishedVersion

To enhance osseointegration in total hip arthroplasty (THA), ultraporous or highly porous-coated cups were introduced. Implant survival data on these new devices have been scarce. The aim of our study was to assess the survivorship of ultraporous Tritanium cups (Stryker) in a population-based register study.In this study, we collected data on 6,080 primary THAs using a Tritanium cup and 25,670 THAs using a conventional cup (control group) from the Finnish Arthroplasty Register; these procedures were performed from January 1, 2009, to December 31, 2017. We calculated the Kaplan-Meier survival estimates with 95% confidence intervals (CIs). The end point was revision for any reason or for aseptic loosening of the cup. The revision risks were assessed with use of the Cox multiple regression model. The variables assessed in the Cox model were femoral head size, age group, involved side, operation year, sex, diagnosis, and fixation of the stem. The proportional hazards assumption of the Cox model was not fulfilled, so the follow-up time was divided into 3 time periods: 0 to 2 years,2 to 4 years, and4 years.When comparing the 2 groups with regard to revision for any reason, the 5-year Kaplan-Meier survivorship of the Tritanium group (94.7% [95% CI, 94.0% to 95.4%]) was inferior to that of the control group (96.0% [95% CI, 95.7% to 96.3%]). In the Cox regression analysis of the 2 groups for the time period of4 years, the Tritanium group had an increased risk of revision for any reason compared with the control group (hazard ratio [HR], 3.12 [95% CI, 1.82 to 5.35]; p0.001). With regard to revision for aseptic loosening of the cup, the Tritanium group had an increased risk of revision compared with the control group for both 0 to 2 years (HR, 3.80 [95% CI, 1.76 to 8.24]; p0.001) and2 to 4 years (HR, 11.2 [95% CI, 3.28 to 38.0]; p0.001).There was no advantage to using the ultraporous-coated Tritanium cup for primary THA compared with conventional uncemented cups. However, wide CIs for some HR estimates may point to a lack of precision. Therefore, further research on subject is needed.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Articular cartilage defects caused by traumatic injury rarely heal spontaneously and predispose into post-traumatic osteoarthritis. In the current autologous cell-based treatments the regenerative process is often hampered by the poor regenerative capacity of adult cells and the inflammatory state of the injured joint. The lack of ideal treatment options for cartilage injuries motivated the authors to tissue engineer a cartilage tissue which would be more resistant to inflammation. A clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout of TGF-beta-activated kinase 1 (TAK1) gene in polydactyly chondrocytes provides multivalent protection against the signals that activate the pro-inflammatory and catabolic NF-kappa B pathway. The TAK1-KO chondrocytes encapsulate into a hyaluronan hydrogel deposit copious cartilage extracellular matrix proteins and facilitate integration onto native cartilage, even under proinflammatory conditions. Furthermore, when implanted in vivo, compared to WT fewer pro-inflammatory M1 macrophages invade the cartilage, likely due to the lower levels of cytokines secreted by the TAK1-KO polydactyly chondrocytes. The engineered cartilage thus represents a new paradigm-shift for the creation of more potent and functional tissues for use in regenerative medicine., Advanced Healthcare Materials, 12 (17), ISSN:2192-2640, ISSN:2192-2659

Background: Cementless unicondylar knee arthroplasty (UKA) was introduced to secure longterm fixation and reduce the risk of revision. Experience with cementless UKA fixation is limited. Methods: The short-term survival (up to five years) of cementless Oxford UKA was assessed using data from the Finish Arthroplasty Register and was compared with that of cemented Oxford 3 UKA and total knee arthroplasty (TKA). Datawere obtained, from the Finnish Arthroplasty Register, on 1076 cementless Oxford UKAs and 2279 cemented Oxford 3 UKAs performed for primary osteoarthritis in 2005-2015. The Kaplan-Meier method, with revision for any reason as the endpoint, was used to assess the survival of these two UKA groups, and the results were compared with that of 65,563 cemented TKAs treated for primary osteoarthritis over the same period. The risk of revision of both Oxford prostheses was compared using Cox regression model, with adjustment for age and sex, with the cemented TKA group as reference. Results: The three-year survival was 93.7% for the cementless Oxford, 922% for the cemented Oxford 3, and 97.3% for the cemented TKA. The corresponding figures at five years were 92.3%, 88.9%, and 96.6%, respectively. The revision rate for both the cementless Oxford and the cemented Oxford 3 was significantly increased when compared with the cemented TKA (P

1D axial dispersion and 3D CFD models for the extraction of levulinic acid from dilute aqueous solution by applying 2-methyltetrahydrofuran as a solvent are presented. The models are validated by comparison with the measured levulinic acid concentration profile data obtained in a bench-scale Kühni column. The 1D model contains NRTL parameters for the system levulinic acid-water-2MTHF. Correlations for drop size and hold-up for Kühni columns were taken from literature. The values for overall mass transfer coefficient ranged from 1.4E-5 to 2.2E-5 ms −1 , and increased as a function of the rotor speed. The fitting of the column performance resulted in a very good prediction of the solute concentration profiles in the extraction column, and the average absolute value of relative error for the 1D model was 23%. CFD model visualized the column performance at the column height of 150.5–160 cm giving valuable information on back mixing, phase velocities, dispersed phase volume fraction, and mass transfer. Dispersed phase volume fraction and mass transfer contours revealed, that the mass transfer rate (app. 0.25 g L −1 s −1 )is at its highest just below the rotor, and that there are blind spots in the compartments close to the extractor and just above each down comer. Values for the dispersed phase volume fraction are highest in the same area where the mass transfer reaches the highest values. The highest slip velocity values (app. 0.03 m −1 )are located in the tip of each compartment partition plates. General correlations, such as hold-up and drop size correlations, can successfully be applied in levulinic acid-water-2MTHF system reported in this work. The 1D axial dispersion model proved to be valuable tool for scale-up purposes, and CFD model, despite the long time needed for each simulation, gave useful information for the design purposes.

Aseptic loosening of total joint replacements is driven by a macrophage-mediated inflammatory reaction to implant-derived wear particles. Phagocytosis of implant debris has been suggested to activate the NLRP3 inflammasome leading to secretion of interleukin (IL)-1β. However, factors and molecular mechanisms driving the particle-induced inflammasome activation are yet to be fully elucidated. In this study, we investigated the inflammasome response of human primary macrophages to titanium, chromium, and molybdenum particles in vitro. We observed that particles alone were not sufficient to induce IL-1β secretion, but an additional priming signal—such as bacterial lipopolysaccharide (LPS)—was required to license the inflammasome activation. By using specific inhibitors against the inflammasome signaling pathway, we demonstrate that the particle-induced IL-1β secretion depended upon activation of the NLRP3 inflammasome. We further hypothesized that tumor necrosis factor (TNF) could substitute for LPS as a priming signal, and found that particle stimulation together with preceding TNF treatment resulted in inflammasome-dependent IL-1β production as well. Our results show that the NLRP3 inflammasome mediates wear particle responses in human primary macrophages, and its activation does not necessarily require the presence of bacterial components, but can be induced under aseptic conditions by TNF priming. Statement of Significance This study was conducted to elucidate the molecular mechanisms of metal particle-induced IL-1β secretion in human primary macrophages. Production of this pro-inflammatory mediator from wear particle-activated macrophages has been associated with increased bone loss around total joint replacements—a condition eventually requiring revision surgery. Our results confirm that together with a co-stimulatory priming signal, particles of common implant metals elicit macrophage-mediated IL-1β secretion through activation of the NLRP3 inflammasome pathway. We also present a concept of TNF priming in this context, demonstrating that the particle-related IL-1β secretion can take place in a truly sterile environment. Thus, inhibition of inflammasome signaling appears a means to prevent wear particle-induced inflammation and development of peri-prosthetic osteolysis.

Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. In particular, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by alarmins (also known as danger signals) are thought to be involved. Thus, toll-like receptors (TLRs) and their signaling pathways are of particular interest. Recent reports suggest that among the TLR-induced innate immune responses, apoptosis is one of the critical events. Apoptosis is of particular importance, given that chondrocyte death is a dominant feature in OA. This review focuses on the role of TLR signaling in chondrocytes and the role of TLR activation in chondrocyte apoptosis. The functional relevance of TLR and TLR-triggered apoptosis in OA are discussed as well as their relevance as candidates for novel disease-modifying OA drugs (DMOADs).

BACKGROUND: Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown. STUDY DESIGN AND METHODS: In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma. We used rivaroxaban-spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator to induce clot lysis. RESULTS: Rivaroxaban resulted in a hypocoagulant state that remained largely unaltered upon subsequent 50% dilution with S/D-treated plasma or FFP. Using S/D-treated plasma as a diluent, clot stability decreased due to its low α2-antiplasmin. Dilution with saline and albumin induced a profibrinolytic state and further deteriorated the impaired hemostatic potential of rivaroxaban-anticoagulated blood, even after PCC and fibrinogen support. Combined use of plasma (either FFP or S/D treated) and PCC, however, considerably improved both coagulation and clot stability. CONCLUSION: In the setting of rivaroxaban anticoagulation and major blood loss, transfusing plasma together with PCC may provide the most effective resuscitation approach with the notion that additional antifibrinolytic drug support (e.g., tranexamic acid) is likely required.

BACKGROUND: Large-diameter head metal-on-metal (MoM) THA has largely been abandoned as a result of higher than anticipated revision rates. However, the majority of these implants are still in situ. Although earlier reports from the Finnish Arthroplasty Register noted similar short-term survivorship between large-diameter head MoM THA and conventional cemented THA, longer term survivorship of this population is unclear. Although reported revision rates for this implant group have been high, the majority of these implants have not been revised and followup is important to improve long-term management. QUESTIONS/PURPOSES: The purposes of this study were (1) to compare the 10-year competing risk survivorship of large-diameter head MoM THA with the survivorship of conventional THA in the Finnish Arthroplasty Register; (2) to report the large-diameter head MoM THA survival at the manufacturer/brand level; and (3) to identify the most common reasons for revision of large-diameter head MoM THA in the Finnish Arthroplasty Register. METHODS: The six most commonly used large-diameter head (≥ 38 mm) MoM THA devices in Finland between years 2004 and 2013 were selected (n = 10,959 implants). The completeness of the Finnish Registry is > 95% in primary THA and patients are censored from the date of death or at the point of emigration; followup continued until the end of 2015. The conventional THA control group consisted of the two most frequently used devices (Vision/Bimetric and ABG II/ABG II) with metal-on-polyethylene or ceramic-on-ceramic bearing surfaces implanted between 2002 and 2013 (n = 5177). The study group was formed by selecting all pairs of large-diameter head MoM and reference THA protheses within the same age group ( < 49, 50-54, 55-59, 60-64, 65-69, 70-74, and 75+ years), sex, diagnosis (osteoarthritis, other), and hospital yearly operation count (< 100 operations yearly, ≥ 100 operations yearly); 5166 matched pairs were identified. Revision for any reason was considered as the failure endpoint of followup. Implant survival (the proportion not revised) was calculated from corresponding cumulative incidence function adjusted for patient death as a competing event for revision. Large-diameter head MoM implant group revision hazard ratios with 95% confidence intervals were estimated with age group, sex, diagnosis, and hospital yearly operation count as confounding factors in a Cox regression model. RESULTS: Ten-year survivorship free from all-cause revision was lower for THAs that used a large-diameter femoral head than it was for the control group of conventional THA (83% [95% confidence interval {CI}, 82%-84%] versus 92% [95% CI, 91%-93%]). At the implant level, every large-diameter head MoM THA had a higher risk for revision compared with the conventional THA control group from the fourth postoperative year onward. The highest survival of MoM THA was 88% (95% CI, 86%-90%) for the ReCap/Bimetric and the lowest survival was 46% (95% CI, 41%-51%) for the recalled ASR with either the Summit® or Corail® stem. The most common revision reason in the MoM THA group was adverse reaction to metal debris, whereas dislocation was predominant in the conventional THA control group. CONCLUSIONS: The revision rate for all large-diameter head MoM THAs in this timeframe in the Finnish Arthroplasty Register is unacceptably high and in our view supports the decision to abandon their use. In agreement with the directives of other national organizations, we recommend regular followup of all patients with large-diameter head MoM THA. Based on our results, strict guidelines for followup should be maintained over the lifetime of the implant to assess patient symptoms and recommend revision when indicated. LEVEL OF EVIDENCE: Level III, therapeutic study.

BACKGROUND: Survival of cruciate-retaining (CR) TKA is generally good, but there may be important differences in survivorship among devices, and different designs may not all be equally patellar-friendly. Large registry databases are needed to identify small but important differences between devices. QUESTIONS/PURPOSES: The purposes of this study were (1) to assess the long-term survivorship of the most common CR TKA devices with revision for any reason as the endpoint and compare the revision risk of these devices after controlling for the potentially confounding variables of age, sex, hospital volume, and primary diagnosis; and (2) to analyze these same devices with revision for secondary resurfacing of the patella as a separate endpoint. METHODS: Data were collected from the Finnish Arthroplasty Register. Over 95% of all primary TKAs are captured in the Finnish Register. We assessed Kaplan-Meier (KM) survivorship for each of the four most frequently used CR TKA designs used between years 2005 and 2015: Triathlon CR (n = 34,337), Nexgen CR Flex (n = 15,723), PFC Sigma CR (n = 15,541), and Vanguard CR (n = 9461), with revision for any reason as the endpoint. Revision was defined as a reoperation in which at least one of the components was exchanged (including insert exchange). Revisions in which the patella was not resurfaced at the primary operation and was resurfaced in the revision were studied as a separate endpoint. The mean followup times were 4.0 (range, 0-11.0) years for Triathlon CR, 3.8 (range, 0-11.0) years for Nexgen CR Flex, 5.1 (range, 0-11.0 ) years for PFC Sigma CR, and 4.9 (range, 0-10.9) years for Vanguard CR (p < 0.001). The group demographics were clinically comparable. We compared the risk of revision of these devices in the Cox multiple regression model with adjustment for hospital volume, age, sex, and primary diagnosis. There were some differences in the incidence of patellar resurfacing at the time of index arthroplasty (Nexgen CR flex 18.7%, PFC Sigma CR 18.4%, Triathlon CR 11.3%, Vanguard CR 14.4%), which was controlled by the Cox model. Implant survival analyses for Triathlon CR, Nexgen CR Flex, and PFC Sigma CR were also performed at the hospital level for the 25 largest TKA providers in Finland. RESULTS: The overall 10-year KM survivorships were 96% (95% confidence interval [CI], 95-96) for Nexgen CR Flex, 96% (95% CI, 96-97) for PFC Sigma CR, 94% (95% CI, 93-95) for Triathlon CR, and 94% (95% CI, 93-95) for Vanguard CR. After controlling for potential confounding variables like age, sex, hospital volume, and primary diagnosis, both Triathlon CR (hazard ratio [HR], 1.4; 95% CI, 1.2-1.6; p < 0.01) and Vanguard CR (HR, 1.4; 95% CI, 1.2-1.6; p < 0.01) had an increased risk for revision compared with the Nexgen CR Flex (the reference device). When revision with patellar resurfacing served as the endpoint, after controlling for those same confounding variables, Triathlon CR had a higher risk for revision than Nexgen CR Flex (HR, 1.8; 95% CI, 1.4-2.2; p < 0.01). CONCLUSIONS: Despite slight differences among the studied devices, the overall 10-year survivorship of the current devices studied was good. However, there were differences in implant survival between the study devices, especially when revision for late patellar resurfacing was analyzed. Further studies adjusted for additional hospital and surgeon variables will be needed to examine and confirm our results. LEVEL OF EVIDENCE: Level III, therapeutic study.

BACKGROUND: Uncontrollable bleeding is the leading cause of death in traumatically injured patients. The extent to which direct factor Xa inhibitors interfere with the applied resuscitation measures is presently unknown. STUDY DESIGN AND METHODS: In this study, we investigated the effect of the resuscitation fluids saline, albumin, fresh frozen plasma (FFP) and solvent/detergent (S/D)-treated plasma, fibrinogen concentrate, prothrombin complex concentrate (PCC), and combinations thereof on the hemostatic profile of rivaroxaban-anticoagulated whole blood and plasma. We used rivaroxaban-spiked whole blood and plasma from healthy donors, as well as plasma from patients on rivaroxaban, and mimicked a resuscitation approach in a 50% plasma dilution setting. Thromboelastography, thrombin generation, and fibrin generation clot lysis test were assessed using tissue factor to initiate coagulation and tissue plasminogen activator to induce clot lysis. RESULTS: Rivaroxaban resulted in a hypocoagulant state that remained largely unaltered upon subsequent 50% dilution with S/D-treated plasma or FFP. Using S/D-treated plasma as a diluent, clot stability decreased due to its low α2-antiplasmin. Dilution with saline and albumin induced a profibrinolytic state and further deteriorated the impaired hemostatic potential of rivaroxaban-anticoagulated blood, even after PCC and fibrinogen support. Combined use of plasma (either FFP or S/D treated) and PCC, however, considerably improved both coagulation and clot stability. CONCLUSION: In the setting of rivaroxaban anticoagulation and major blood loss, transfusing plasma together with PCC may provide the most effective resuscitation approach with the notion that additional antifibrinolytic drug support (e.g., tranexamic acid) is likely required.

The precipitation process of L-glutamic acid from monosodium glutamate solution through acidification is studied by using hydrochloric acid and sulphuric acid. Both experimental and modelling methods are applied. The experiments have been carried out with a single feed semi-batch process applying two acid feed rates and two rotational mixing speeds. The method for computational fluid dynamics (CFD) modelling of the semi-batch process with a changing fluid volume is presented. The precipitation process including nucleation and crystal growth is modelled with CFD by using the kinetics presented in the literature for hydrochloric acid. A model for agglomeration presented in the literature and Eddy Dissipation Concept for micromixing are applied in the case of a lower rotational speed and hydrochloric acid. The particle size distribution is modelled with the simple number density model and with Quadrature Method of Moments. Micromixing was found to have an insignificant effect, but when including the model for agglomeration, the particle size distribution was in better agreement with the experiments. However, pH evolution of the system was captured better without the agglomeration model, indicating that the kinetic model may not describe the precipitation accurately. The pH and saturation ratio Sα were modelled based on thermodynamics. The significance of activities is highlighted in computing the thermodynamic equilibrium, and in precipitation kinetics. It was found that the applied acid had an effect on the chemical process, although the species concentrations were the same. The difference of the kinetic models between hydrochloric acid and sulphuric acid could be explained by the more complex dissociation of sulphuric acid. The greater computational ionic strength with sulphuric acid increased the nucleation rate, resulting in a difference in pH evolution in comparison with hydrochloric acid. Therefore, the kinetic parameters determined for the hydrochloric acid system are not applicable for other acid systems with different chemical compositions. For the modelling of the precipitating systems, more experimental work is needed for determining the kinetics.

Background and purpose — 7% of the asymptomatic population has leg-length inequality (LLI) greater than 12 mm. It has been proposed that LLI of >5 mm can be associated with an increased risk of osteoarthritis (OA) of the knee and hip. We studied a possible association between LLI and OA of the knee and hip joint. Patients and methods — We followed 193 individuals (97 women, 96 men) for 29 years. The initial mean age of the participants was 43 (34–54) years, and they had no clinical histories or signs of leg symptoms. The initial standing radiographs of their hips were re-examined and measured for LLI and signs of OA. None had any signs of OA. At the follow-up, data on performed hip or knee arthroplasties were obtained. Results — 24 (12%) of the subjects had no discernible leg-length difference, 62 (32%), had LLIs of 1–4 mm, 74 (38%) of 5–8 mm, 21 (11%) of 9–12 mm, and 12 (6%) of over 12 mm. 16 (8%) of the subjects had undergone arthroplasty for primary OA during follow-up, and of those, 8 for both hip and knee OA. 10 individuals had undergone an arthroplasty of the longer leg and only 3 of the shorter leg. In the group of equal leg length, 3 had had an arthroplasty of hip or knee. Interpretation — We noted that hip or knee arthroplasty due to primary OA had been done 3 times more often to the longer leg than to the shorter.

Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2-8) and day 28 post-operation. APTT and PT were immediately analysed. Calibrated anti-FXa activity, Russel's Viper Venom Time (RVVT) and thrombin generation (TG; Calibrated Automated Thrombogram(A (R))) captured the effects of FXaI on coagulation and TG. APTT and PT remained within the reference interval throughout, and did not correlate with FXaI levels (PT R-2 = 0.44, APTT R-2 = 0.07). Mean apixaban concentration at the peak varied by eightfold (19-153 ng/mL), but rivaroxaban only by 1.5-fold (111-183 ng/mL). Rivaroxaban, but not apixaban prolonged RVVT at peak levels. Both FXaIs had a prolonged lag time of TG (p

Background: Constrained acetabular devices were developed to prevent dislocations after total hip arthroplasty (THA). However, the data on their success have been contradictory. In this study, we aimed to assess implant survival of the constrained acetabular device in primary THA based on the Finnish Arthroplasty Register data. Methods: A total of 373 primary THAs with constrained acetabular devices inserted from 2006 to 2017 were included. A reference group was formed on a 1:3 basis and matched for age, sex, and diagnosis, consisting of 1118 conventional THAs. Implant survival estimates using death as a competing risk were assessed with revision for any reason and for any aseptic reason as the endpoints. The Cox multiple regression models were adjusted for age, sex, and diagnosis. The mean follow-up time was 3.3 (0-12.4) years for the constrained device group and 3.8 (0-12.0) years for the reference group. Results: Overall, there were 21 revisions in the constrained device group and 49 in the reference group. The 8-year survivorship for any reason was 94% (confidence interval [CI]: 91-96) for the constrained device group and 93% (CI: 89-97) for the reference group. With revision for any aseptic reason as the endpoint, the 8-year survivorships were 97% (CI: 95-99) and 94% (CI: 90-98), respectively. During the first 1.5 years, the constrained acetabular device group had a similar revision risk (hazard ratio: 1.09 [CI: 0.57-2.07], P = .8) to that of the reference group. Conclusion: The constrained acetabular device had good survival in primary THA, and our results support its continued use even in high-risk patients. (C) 2019 The Authors. Published by Elsevier Inc.

Background and purpose — The use of trabecular metal (TM) cups for primary total hip arthroplasty (THA) is increasing. Some recent data suggest that the use of TM in primary THA might be associated with an increased risk of revision. We compared implant survival of Continuum acetabular cups with other commonly used uncemented cups. Patients and methods — Data on 11,390 primary THAs with the Continuum cup and 30,372 THAs with other uncemented cups (reference group) were collected from the Finnish Arthroplasty Register. Kaplan–Meier survival estimates were calculated; the endpoint was revision for any reason, for infection, or for dislocation. Revision risks were assessed with adjusted Cox multiple regression models. A subgroup analysis on the use of neutral or elevated liners in the Continuum group was made. Results — The 7-year survivorship of the Continuum group was 94.6% (95% CI 94.0–95.2) versus 95.6% (CI 95.3–95.8) in the reference group for revision for any reason. The risk for revision was higher in the Continuum group than in the reference group both for revision for any reason (HR 1.3 [CI 1.2–1.5)]) and for revision for dislocation (HR 1.9 [CI 1.5–2.3]). There was no difference in the rates of revision because of infection (HR 0.99 [CI 0.78–1.3]). Use of a neutral liner increased the risk for revision due to dislocation in comparison with the use of an elevated rim liner in the Continuum group (HR 1.7 [CI 1.2–2.5]). Interpretation — THA with Continuum cups is associated with an increased risk of revision compared with other uncemented cups, mainly due to revisions because of dislocation. Our results support the use of an elevated liner when Continuum cups are used for primary THA.

Supersaturation of inversely soluble salts, like calcium carbonate, causes crystallization fouling on heated surfaces of heat exchangers. In this paper, crystallization fouling of calcium carbonate is studied by CFD modelling. Crystallization fouling is modelled in 2D and 3D flat plate geometries, which correspond to an experimental set-up of an idealised heat exchanger. The model is validated with experimental data under various operating conditions and is used to identify the regions where different parameters have the greatest effect on fouling. The CFD model presented in this paper is a novel combination of a fouling model, which includes the surface integration term and the shear stress dependent residence time, and the hydrodynamics and heat transfer modelled by CFD. The crystallization fouling CFD model predicts the experimental mass deposition rate and the linear fouling resistance within the experimental uncertainty in most of the studied conditions. The crystallization fouling CFD model is very sensitive to the heat exchanger surface temperature, but also relatively sensitive to the shear stress. The validated crystallization fouling model may be utilised to study fouling of industrial heat exchangers when the fouling is controlled by the surface integration. If mass transfer controls the crystallization fouling, the mass transport of ions should be included to the model.

Because of the increasing number of total hip arthroplasties (THAs), even a small proportion of complications after the operation can lead to substantial individual difficulties and health-care costs. The aim of this study was to develop simple-to-use risk prediction models to assess the risk of the most common reasons for implant failure to facilitate clinical decision-making and to ensure long-term survival of primary THAs. Methods: We analyzed patient and surgical data reported to the Finnish Arthroplasty Register (FAR) on 25,919 primary THAs performed in Finland between May 2014 and January 2018. For the most frequent adverse outcomes after primary THA, we developed multivariable Lasso regression models based on the data of the randomly selected training cohort (two-thirds of the data). The performances of all models were validated using the remaining, independent test set consisting of 8,640 primary THAs (one-third of the data) not used for building the models. Results: The most common outcomes within 6 months after the primary THA were revision operations due to periprosthetic joint infection (1.1%), dislocation (0.7%), or periprosthetic fracture (0.5%), and death (0.7%). For each of these outcomes, Lasso regression identified subsets of variables required for accurate risk predictions. The highest discrimination performance, in terms of area under the receiver operating characteristic curve (AUROC), was observed for death (0.84), whereas the performance was lower for revisions due to periprosthetic joint infection (0.68), dislocation (0.64), or periprosthetic fracture (0.65). Conclusions: Based on the small number of preoperative characteristics of the patient and modifiable surgical parameters, the developed risk prediction models can be easily used to assess the risk of revision or death. All developed models hold the potential to aid clinical decision-making, ultimately leading to improved clinical outcomes. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. publishedVersion

The advantages of synthetic bone graft substitutes over autogenous bone grafts include abundant graft volume, lack of complications related to the graft harvesting, and shorter operation and recovery times for the patient. We studied a new synthetic supercritical CO2 -processed porous composite scaffold of -tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone graft substitute in a rabbit calvarial defect. Bilateral 12mm diameter critical size calvarial defects were successfully created in 18 rabbits. The right defect was filled with a scaffold moistened with bone marrow aspirate, and the other was an empty control. The material was assessed for applicability during surgery. The follow-up times were 4, 12, and 24 weeks. Radiographic and micro-CT studies and histopathological analysis were used to evaluate new bone formation, tissue ingrowth, and biocompatibility. The scaffold was easy to shape and handle during the surgery, and the bone-scaffold contact was tight when visually evaluated after the implantation. The material showed good biocompatibility and its porosity enabled rapid invasion of vasculature and full thickness mesenchymal tissue ingrowth already at four weeks. By 24 weeks, full thickness bone ingrowth within the scaffold and along the dura was generally seen. In contrast, the empty defect had only a thin layer of new bone at 24 weeks. The radiodensity of the material was similar to the density of the intact bone. In conclusion, the new porous scaffold material, composed of microgranular -TCP bound into the polymer matrix, proved to be a promising osteoconductive bone graft substitute with excellent handling properties [GRAPHICS]

BACKGROUND The aim of our prospective, multicenter, randomized, controlled trial (titled M2A-38 Ceramic-on-Metal RCT, NCT00754520) is to demonstrate noninferiority of a ceramic-on-metal (CoM) articulation compared with metal-on-metal (MoM) in total hip arthroplasty. The study arms are at 8 years since implantation, with metal ion and functional score analysis at 5 years. METHODS We recruited 211 patients between 2009 and 2011. The patients were randomized to ceramic or metal. A cohort of these patients had whole blood metal ions performed yearly, and all patients underwent annual radiographic and clinical outcome assessment. All revisions were recorded and some explants were analyzed. Recruitment ceased earlier than planned owing to concerns raised with failure of MoM implants. RESULTS No significant difference was seen in patient demographics, radiographic parameters, or functional outcomes at any time point. Lower cobalt ion levels were seen in the CoM group (P < .01) at all time points. Chromium levels were significantly lower in the CoM group up to 3 years, but raised at 5 years. There were slightly fewer revisions for adverse reaction to metal debris in the CoM group. Explant analysis suggested a different wear pattern to those seen in the MoM group. CONCLUSION The results demonstrated that the CoM articulation behaved the same as the MoM in terms of functional outcome and radiographic parameters. The CoM coupling also demonstrates raised metal ions beyond 3 years and increasing revisions for adverse reaction to metal debris. It remains difficult to see a clinical application for CoM and further exploration or use is not warranted.

Background The paper reports extensive CFD work and analyses of an oscillatory baffled reactor (OBR) planned to be used for the production of polyaniline continuously. In the polyaniline process, viscosity changes during the course of the reaction. Two non-Newtonian fluids were used to represent the stages of fluids during the reaction in a simulation, in addition to water as the reference fluid. Two quantitative measures derived from the CFD results are employed to evaluate OBR reactor performance: the axial dispersion coefficient and the ratio of axial and transverse velocities. Results The CFD data showed that the dispersion coefficient as a function of viscosity exhibits a maximum for given oscillation parameters. In the turbulent regime, the axial dispersion is often correlated with the oscillatory Reynolds number in OBR or equivalent Reynolds numbers in other reactor devices. In the high viscosity regime, such a general correlation is not valid for different operational parameters. The results of the CFD simulations in the moving baffle-OBR indicate, for the first time, that the axial dispersion coefficients in the moving baffle arrangement is 10–17% higher than that in the moving fluid type, due to enhanced shear rate in the former device. This quantitative information is valuable for the design and smooth transition from batch to continuous reactors. Conclusion The established dependence of axial dispersion and the ratio of axial to transverse velocities on both viscosity and the operational parameters enhanced the understanding of mixing and dispersion characteristics of the OBR. The CFD analysis supplied the information needed to determine the design parameters for the reactor used in continuous production of polyaniline.© 2012 Society of Chemical Industry

Comprehensive CFD-model for reactive flow of gas and liquid in porous catalyst beds was developed and numerically tested. The three phase trickle-bed process involving both gas and liquid phases and the fixed bed of porous catalyst particles includes hydrodynamic forces, mechanical and capillary dispersion, and wetting efficiency. In the present work, the model was extended to include reactions, mass transfer and heat transfer. The stationary gas and liquid inside the porous particles were modeled separately from the bulk gas and liquid phases flowing outside the particles, with convective and diffusive mass transfer between the inner and outer fluids. Reactions were assumed to take place inside the catalyst particles. The process modeled in this work was the hydrogenation of octene in Ni/Al2O3 reactor. The reaction is highly exothermic resulting in evaporation and condensation of the components. All submodels were implemented in Fluent software. Numerical tests were carried out to show that the CFD model allows the investigation of local variations in the reactor, caused for example by bed drying or the effects of irregular liquid feed.

CFD simulations of trickle-bed reactors are presented with radial spreading of the liquid due to mechanical and capillary dispersion. Simulations are performed with various particle sizes and the significance of the dispersion mechanisms at the industrially relevant particle size range is analyzed. The effect of the bed porosity distribution and particle size to the simulation results is also discussed. The choice of the radial porosity profile is found to have a significant impact to the simulation results, especially when the column to particle diameter ratio, D/dp, is small, in which case the wall flow is important. The dependence of the standard deviation of porosity on the sample size is determined experimentally. Introducing just random variation of porosity to the model is found to describe inadequately the dispersive flow behavior. The presented hydrodynamic model with proper capillary and mechanical dispersion terms succeeds in capturing the features of the two independent physical phenomena. Separate models are presented for each dispersion mechanisms and it is shown that they both can have a significant contribution to the overall dispersion of liquid flowing through a packed bed. The hydrodynamic model is validated against the experimental dispersion profiles from Herskowitz and Smith [1978. Liquid distribution in trickle-bed reactors. A.I.Ch.E Journal 24, 739–454], Boyer et al. [2005. Study of liquid spreading from a point source in trickle-bed via gamma-ray tomography and CFD simulation. Chemical Engineering Science 60, 6279–6288] and Ravindra et al. [1997. Liquid flow texture in trickle-bed reactors: an experimental study. Industrial & Engineering Chemistry Research, 36, 5133–5145]. The extent of liquid dispersion predicted by the presented hydrodynamic model is in excellent agreement with the experiments.

An improved hydrodynamic model is developed for estimating wetting efficiency, pressure drop, and liquid holdup in trickle-bed reactors. The model is based on the hydrodynamic model presented in Alopaeus et al. [Alopaeus, V.; Hynynen, K.; Aittamaa, J.; Manninen, M. Modeling of Gas−Liquid Packed-Bed Reactor with Momentum Equations and Local Interactions Closures. Ind. Eng. Chem. Res. 2006, 45, 8189.], which is extended to take into account partial wetting of the packing. In addition, the applicability of the 1D model for three-dimensional situations is considered in the process of model development. The wetting efficiency model is formulated on the basis of dimensional analysis and carrying out systematic tests with varying combinations of dimensionless groups. In addition, the wetting efficiency model is not evaluated solely on the wetting efficiency data, but also it is tested systematically with the hydrodynamic model. Furthermore the consistency of the model characteristics to common experimental observations is discussed. Finally, the model’s ability to predict wetting efficiency, dimensionless pressure drop, and liquid saturation was compared to other existing models and improvements were found in all areas. The resulting hydrodynamic model can be used equally as a tool for design and modeling of large scale industrial reactors as well as a tool for complicated three-dimensional simulations.

The treatment of fractures of the distal third of the tibia remains still controversial. It is often difficult to get and retain good reduction by non-operative or nailing methods. Open reduction and plate fixation offers good reduction and retention of the achieved position. However, increased soft tissue damage and high complication rate has led to search less invasive surgical methods such as minimal invasive plating technique.Lateral approach for the distal tibia allows to reduce and to plate both the fibula and the tibia using only one skin incision. We have used lateral approach for 20 consecutive tibia fracture patients and report clinical and radiological results after an average follow-up of 31 months.All fractures united, but two malunions were developed after good primary reduction. Seventeen patients achieved excellent or good subjective result while one had moderate and two poor results. Four superficial wound infections were noticed and they were treated conservatively.We conclude that lateral approach for the distal tibia is a demanding, but useful surgical method for treatment of the distal tibia fractures especially in cases where no medial comminution of the tibia is present and when the fibula has to be fixed, too.

To determine the extent of asymmetrical deficits in knee extensor and flexor muscles, and to examine whether asymmetrical muscle deficits are associated with mobility limitations in persons with late-stage knee osteoarthritis (OA).Cross-sectional.Research laboratory.A clinical sample (N=56; age range, 50-75y) of eligible persons with late-stage knee OA awaiting knee replacement.Not applicable.Knee extensor and flexor power and torque assessed isokinetically; thigh muscle cross-sectional area (CSA) assessed by computed tomography; mobility limitation assessed by walking speed and stair ascension time; and pain assessed with the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire.The asymmetrical deficits in knee extensor and flexor power and torque were between 18% and 29% (P.001). Regarding the thigh muscle CSA, the asymmetrical deficit was 4% (P.001). Larger asymmetrical knee extensor power deficits and weaker knee extensor and flexor power on the contralateral side were associated with slower stair ascension times. Moreover, weaker knee extensor and flexor power on the ipsilateral side were associated with slower stair ascension times. Greater knee pain in the OA joint was independently associated with slower stair ascending time in both models.The knee extensor and flexor muscle power of both the ipsilateral and contralateral sides and the pain in the OA knee were independently associated with stair ascension times. These results highlight the importance of assessing muscle power on both sides and knee pain in the prevention of mobility limitations in patients with knee OA.

A computational fluid dynamics (CFD) model for particulate fouling in heat exchangers has been developed. Particulate fouling is generally considered as a serial process of the transport of the particles into the vicinity of the wall and the adherence on the surface. Particle adhesion on the surface is described by a mass transfer coefficient based on the XDLVO theory. For modelling particle transport, the generally accepted models were applied. A wall function approach was developed for calculating the near-wall particle transport in order to avoid the use of excessively small computational cells. The model is based on the assumption of local equilibrium of the forces affecting the particle transport. The wall function model is compared to a detailed CFD model and to experimental results from a fouling test apparatus using the assumption of a smooth and already fouled surface. Comparisons were made with several heat fluxes and mass flow rates applying various high concentrations of colloidal calcium carbonate (CaCO 3 ) particles suspended in water. Results of simulations are in fairly good agreement with measurements. The wall function model allows the applications of coarser computational grids and therefore modelling of practical industrial heat exchangers.

International audience; Capillary pressure is considered in packed-beds of spherical particles. In the case of gas-liquid flows in packed-bed reactors, capillary pressure gradients can have a significant influence on liquid distribution and, consequently, on the overall reactor performance. In particular, capillary pressure is important for non-uniform liquid distribution, causing liquid spreading as it flows down the packing. An analytical model for capillary pressure-saturation relation is developed for the pendular and funicular regions and the factors affecting capillary pressure in the capillary region are discussed. The present model is compared to the capillary pressure models of Grosser et al. (AIChE J., 34:1850-1860, 1988) and Attou and Ferschneider (Chem. Eng. Sci., 55:491-511, 2000) and to the experiments of Dodds and Srivastava (Part Part Syst. Charact., 23:29-39, 2006) and Dullien et al. (J. Colloid Interface Sci., 127:362-372, 1989). The non-homogeneity of real packings is considered through particle size and porosity distributions. The model is based on the assumption that the particles are covered with a liquid film, which provides hydrodynamic continuity. This makes the model more suitable for porous or rough particles than for non-porous smooth particles. The main improvements of the present model are found in the pendular region, where the liquid dispersion due to capillary pressure gradients is most significant. The model can be used to improve the hydrodynamic models (e.g., CFD and cellular automata models) for packed-bed reactors, such as trickle-bed reactors, where gas, liquid, and solid phases are present. Models for such reactors have become quite common lately (Saez and Carbonell, AIChE J., 31:52-62, 1985; Holub et al., Chem. Eng. Sci, 47, 2343-2348, 1992; Attou et al., Chem. Eng. Sci., 54:785-802, 1999; Iliuta and Larachi, Chem. Eng. Sci., 54:5039-5045, 1999, IJCRE 3:R4, 2005; Narasimhan et al., AIChE J., 48:2459-2474, 2002), but they still lack proper terms causing liquid dispersion.

An algebraic model for the estimation of gas−liquid packed-bed hydrodynamic parameters is developed, based on one-dimensional material and momentum balances for gas and liquid phases. Underlying momentum exchange closures are critically analyzed, which leads to discarding some interaction models between the phases and development of new models based on local hydrodynamics. The present approach is based on more-relevant assumptions for the particle scale geometry than the slit models presented in the literature. The resulting model requires a one-parameter iterative solution, from which both pressure drop and liquid holdup are obtained. The model can be used without any extra complication in situations where the boundary conditions are specified either at the inlet or at the outlet of the reactor. It is suitable for modeling both low- and high-pressure operations, trickling as well as pulsing flow, upflow and downflow arrangements, and processes with Newtonian as well as non-Newtonian liquids. Finally, the present model is compared to its differential counterpart, and to available experimental data from open literature. Reasonably good agreement was observed for both pressure drop and liquid holdup data from a wide range of operating conditions, using only a single set of Ergun parameters.

A systematic study was carried out to investigate the hydrogen behaviour in a BWR reactor building during a severe accident. BWR core contains a large amount of Zircaloy and the containment is relatively small. Because containment leakage cannot be totally excluded, hydrogen can build up in the reactor building, where the atmosphere is normal air. The objective of the work was to investigate, whether hydrogen can form flammable and detonable mixtures in the reactor building, evaluate the possibility of onset of detonation and assess the pressure loads under detonation conditions. The safety concern is, whether the hydrogen in the reactor building can detonate and whether the external detonation can jeopardize the containment integrity. The analysis indicated that the possibility of flame acceleration and deflagration-to-detonation transition (DDT) in the reactor building could not be ruled out in case of a 20 mm2 leakage from the containment. The detonation analyses indicated that maximum pressure spike of about 7 MPa was observed in the reactor building room selected for the analysis.

Ultrasound Doppler Velocimetry (UDV) was successfully applied for measuring the three-dimensional velocity profiles of sand–water slurry in a cylindrical tank equipped with a 45° pitched blade turbine. Radial, axial and tangential velocity components were determined at the middle angular position between two baffles. The flow field in the tank was simulated by employing CFD with an algebraic slip mixture model combined with a sliding mesh method for the impeller. The simulated and measured velocity profiles were compared, and good general agreement between these results was found.

Modelling is one of the most significant prospective tools for design and analysis of trickle-bed reactors. Unfortunately, current hydrodynamic models, developed on laboratory experiments, often work poorly in industrial scale. Therefore, physically, more authentic models are required in which the small-scale phenomena are separated from the large-scale phenomena. This would improve the scale-up of the model and consequently, its applicability to industrial-scale reactors. One of the small-scale phenomena lacking from the current models is radial distribution of liquid. It has not been considered in the model development, although it is commonly thought that liquid flow is radially more uniform in industrial than in laboratory scale. Here, models for liquid distribution, caused by capillary pressure gradients and mechanical dispersion, are suggested and the outline of the implementation of these models to CFD programs is presented. Laboratory experiments and CFD simulations of the experimental setup are performed to gain better understanding about liquid radial distribution. The physical validity of the presented models is assessed on the consistency between the experimental and the modelled liquid flow profiles.

Summary Computational-fluid-dynamics (CFD) modeling of drag reduction (DR) by polymer additives dissolved in hydrocarbon was carried out in pipe flows and in a rotating shear viscometer. A two-layer turbulence model was applied that described turbulence damping by the molecules of drag-reducing additives (DRAs) in the near-wall regions. The von Karman constant in the near-wall region was used as the model parameter. Extensive measurements of the DR effect for a rotating viscometer were performed at different Reynolds numbers, apparent molar masses, and DRA concentrations. The model with only one fit parameter was able to reproduce the experimental results in both pipe flows and the rotating viscometer. Experimental results were used in relating the model parameter to the relevant physical properties.